Analyses of protection mechanisms against Candida albicans infection in various animal models

虽然念珠菌病是在受损宿主中最常见的系统性真菌病，占所有感染的显著百分比，但宿主对感染的防御机制尚未完全了解。两种主要类型的防御机制，一种是非特异性的，一种是特异性的，被认为是对念珠菌病的耐药性负责。本研究的目的是建立一个有效的真菌感染模型，并分析在真菌感染中起重要防御作用的效应细胞。其次，对这些新开发的模型中的各种效应物进行了实际分析，通过这些研究，证实了小鼠静脉或腹腔感染模型仍然是测试各种BRM以及抗真菌化疗药物有效性的有用模型。然而，发现在这些静脉或腹膜内念珠菌， ...更多信息 白念珠菌感染模型中，感染过早而不能显示复杂的宿主防御机制：因此，那些系统性念珠菌模型并不总是适合于研究宿主对感染的抗性的进行性发展。另一个问题是，当小鼠通过静脉注射或腹腔注射途径感染念珠菌时，即使在其他器官中的宿主防御机制已经完全集结力量消灭念珠菌细胞之后，微生物仍在肾脏的连接小管或骨盆中生长。由于肾脏的功能或结构特征，白色念珠菌被认为在肾脏中减少。然而，与这些进行性candemia模型相比，在本研究报道的小鼠大腿病变模型中，小鼠不会因感染而死亡，并且宿主防御机制可以充分发展和运作，而不受其他因素的损害。因此，认为该模型可用于研究感染的组织病理学机制。然而，进一步的研究也表明，小鼠大腿病变模型也有缺点，不适合用于化疗药物的抗真菌活性测试，因为即使是阿替霉素B、氟胞嘧啶或酮康唑在该模型中也不表现出任何活性。利用这些模型进行的研究也表明了不同的效应细胞在不同的感染模型中发挥重要作用以根除真菌成分的可能性，并证实了BRM产生的干扰素和白细胞介素对真菌感染的积极作用。少

Although candidiasis is the most commonly observed systemic mycosis in a compromised host, constituting a significant percentage of all infections, the mechanisms of host defense against the infection have not been fully understood. Two major types of defense mechanisms, one non-specific and one-speci-fic, have been considered responsible for the resistance to candidiasis. In this study, firstly it was aimed to develop useful model for the study of fungal infections and analyses of effector cells which play an important defensive role against fungal infections. Secondly, actual analitic studies of various effectors in these newly developed models using various BRMs(biological response modifiers).Throughout the present studies, it was confirmed that intravenous or intraperitoneal infection models in mice is still useful ones for the test of the effectiveness of various BRMs as well as antifungal chemotherapeutics. However, itwas found that in these intravenous or intraperitoneal Candida … More albicans infection models,infection is too early to manifest complicated host defense mechanisms: therefore, those systemic candemia models are not always suitable for studies of the progressive development of host resistance to the infection. The other problem is that when mice are infected with Candida by the i.v. or i.p. route, the organisms grow in the connecting tubles or in the pelvis of the kidneys even after the host defense mechanisms in other organs have fully marshalled their forces to eradicate the Candida cells The host defense against C. albicans is assumed to be diminished in the kidney due to its functional or structural characteristics. However, compared to these progressive candemia models, in mouse thigh lesion model reported by the present studies, a mouse does not die from the infection, and the host defense mechanisms can fully develop and operate without being impaired by other factors. Therefore, this model was considered to be useful for the study histopathological mechanisms of infections. Further studies, however, also indicated that mouse thigh lesion model has also disadvantages and is not suitable for the test of antifungal activity of chemotherapeutic agents, because even amphotericin B, flucytosine or ketoconazole does not exhibited any activities in this model. Our studies using these models also showed the possibilities that different effector cells play an important role in different infection models for the eradication of fungal elements.Active roles of interferons and interleukins produced by BRMs against fungal infections are also confirmed. Less